A reproducible, non-surgical animal model for low output state resembling cardiogenic shock has been developed in the intact, anesthetized dog. This model is based on the intravenous or intracoronary administration of a pure, myocardial depressor protein (MDP) isolated from the venom of Crotalus atrox. The purpose of this investigation is to elucidate the mechanism and site of action of MDP on the left ventricular myocardium (LVM). Under complete hemodynamic monitoring, MDP will be administered (3.25 mg/kg, IV), the heart excised at 2 hours, and the LVM subjected to detailed biochemical and microscopic analysis. Cardiac cAMP, phosphodiesterase, protein kinase, and myocardial-sarcoplasmic reticulum function studies will yield clues to MDP's mechanism of action. Its site of action will be revealed by light and electron microscopic techniques using standard as well as highly sensitive immunocytochemical and autoradiographic methods. For these studies rabbit antibodies to MDP and radioiodinated (131I) MDP will be used. The molecular structure of MDP, its amino acid sequence, the nature of the active and binding sites and their relationship to its biological activity will also be elucidated. The distinct possibility of synthesizing MDP's active fragment will be considered, and attempts to isolate the cardiac receptor to MDP, by affinity chromatography, will be carried out. The mechanism of action of MDP will also be studied in isolated canine heart and heart-lung preparations. Our ultimate goal is to fully develop a reproducible model in which novel and pre-existing therapeutic regimes to treat the patient with low cardiac output syndrome can be evaluated.